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Neuroendocrine tumors (NETs) are rare neoplasms frequently characterized by an upregulation of the mammalian rapamycin targeting (mTOR) pathway resulting in uncontrolled cell proliferation. The mTOR pathway is also involved in skeletal muscle protein synthesis and in adipose tissue metabolism. Everolimus inhibits the mTOR pathway, resulting in blockade of cell growth and tumor progression. The aim of this study is to investigate the role of body composition indexes in patients with metastatic NETs treated with everolimus. The study population included 30 patients with well-differentiated (G1-G2), metastatic NETs treated with everolimus at the IRCCS Romagnolo Institute for the Study of Tumors (IRST) “Dino Amadori”, Meldola (FC), Italy. The body composition indexes (skeletal muscle index [SMI] and adipose tissue indexes) were assessed by measuring on a computed tomography (CT) scan the cross-sectional area at L3 at baseline and at the first radiological assessment after the start of treatment. The body mass index (BMI) was assessed at baseline. The median progression-free survival (PFS) was 8.9 months (95% confidence interval [CI]: 3.4–13.7 months). The PFS stratified by tertiles was 3.2 months (95% CI: 0.9–10.1 months) in patients with low SMI (tertile 1), 14.2 months (95% CI: 2.3 months-not estimable [NE]) in patients with intermediate SMI (tertile 2), and 9.1 months (95% CI: 2.7 months-NE) in patients with high SMI (tertile 3) (p = 0.039). Similarly, the other body composition indexes also showed a statistically significant difference in the three groups on the basis of tertiles. The median PFS was 3.2 months (95% CI: 0.9–6.7 months) in underweight patients (BMI ≤ 18.49 kg/m2) and 10.1 months (95% CI: 3.7–28.4 months) in normal-weight patients (p = 0.011). There were no significant differences in terms of overall survival. The study showed a correlation between PFS and the body composition indexes in patients with NETs treated with everolimus, underlining the role of adipose and muscle tissue in these patients.

Prostate cancer (PCa) risk categorization based on clinical/PSA testing results in a substantial number of men being overdiagnosed with indolent, early-stage PCa. Clinically non-significant PCa is characterized as the presence of ISUP grade one, where PCa is found in no more than two prostate biopsy cores.MRI-ADC and [68Ga]Ga-PSMA-11 PET have been proposed as tools to predict ISUP grade one patients and consequently reduce overdiagnosis. In this study, Radiomics analysis is applied to MRI-ADC and [68Ga]Ga-PSMA-11 PET maps to quantify tumor characteristics and predict histology-proven ISUP grades. ICC was applied with a threshold of 0.6 to assess the features’ stability with variations in contouring. Logistic regression predictive models based on imaging features were trained on 31 lesions to differentiate ISUP grade one patients from ISUP two+ patients. The best model based on [68Ga]Ga-PSMA-11 PET returned a prediction efficiency of 95% in the training phase and 100% in the test phase whereas the best model based on MRI-ADC had an efficiency of 100% in both phases. Employing both imaging modalities, prediction efficiency was 100% in the training phase and 93% in the test phase. Although our patient cohort was small, it was possible to assess that both imaging modalities add information to the prediction models and show promising results for further investigations.

Predicting clinically significant prostate cancer (csPCa) is crucial in PCa management. 3T-magnetic resonance (MR) systems may have a novel role in quantitative imaging and early csPCa prediction, accordingly. In this study, we develop a radiomic model for predicting csPCa based solely on native b2000 diffusion weighted imaging (DWIb2000) and debate the effectiveness of apparent diffusion coefficient (ADC) in the same task. In total, 105 patients were retrospectively enrolled between January–November 2020, with confirmed csPCa or ncsPCa based on biopsy. DWIb2000 and ADC images acquired with a 3T-MRI were analyzed by computing 84 local first-order radiomic features (RFs). Two predictive models were built based on DWIb2000 and ADC, separately. Relevant RFs were selected through LASSO, a support vector machine (SVM) classifier was trained using repeated 3-fold cross validation (CV) and validated on a holdout set. The SVM models rely on a single couple of uncorrelated RFs (ρ < 0.15) selected through Wilcoxon rank-sum test (p ≤ 0.05) with Holm–Bonferroni correction. On the holdout set, while the ADC model yielded AUC = 0.76 (95% CI, 0.63–0.96), the DWIb2000 model reached AUC = 0.84 (95% CI, 0.63–0.90), with specificity = 75%, sensitivity = 90%, and informedness = 0.65. This study establishes the primary role of 3T-DWIb2000 in PCa quantitative analyses, whilst ADC can remain the leading sequence for detection.

Prostate cancer (PCa) risk categorization based on clinical/PSA testing results in a substantial number of men being overdiagnosed with indolent, early-stage PCa. Clinically non-significant PCa is characterized as the presence of ISUP grade one, where PCa is found in no more than two prostate biopsy cores.MRI-ADC and [

Purpose or Learning Objective To assess the role of radiomic features from high b-value DWI sequences in the early detection of clinically significant prostate cancer (PCa). Methods or Background 76 patients are retrospectively enrolled, who undergo multiparametric MRI (mpMRI) and biopsy examination, where they received a Gleason Score (GS)=3+3 representing non-clinically significant PCa (ncsPCa, n=26) or GS≥3+4 meaning clinically significant PCa (csPCa, n=50). PCa Regions of Interest (ROIs) are outlined on DWI at b=2000s/mm2 and eighty-four local first-order radiomic features are extracted. First, the LASSO-based method selects a subset of relevant features, discarding linearly correlated couples. Then, to prevent overfitting, only the couple with the lowest p-value at Wilcoxon rank-sum test is selected. A Support Vector Machine (SVM) is trained on 48 patients, validated through 3-fold Cross Validation and tested on 28 patients. ROC curve and AUC are used to assess the SVM performance, together with specificity, sensitivity, and Positive Predictive Value (PPV). Results or Findings The AUC of the ROC curve on the training set is 0.86, with specificity and sensitivity equal to 94% and 77%, respectively, whilst the AUC on the test set is 0.84 with specificity and of 75% and 90%, respectively, and PPV=90%. ncsPCa and csPCa are separated with p=0.007. Conclusion The classifier shows a very low probability of overtreatment of ncsPCa while a high PPV strongly improves the performances of clinical mpMRI used in triage pre-biopsy setting. Limitations This study has been carried out on a 3T machine.

Radiomic features (RFs) based on multiparametric MRI (mpMRI) seem promising biomarkers of prostate cancer (PCa), although working with multiple mpMRI sequences makes standardization and proving RFs clinical reliability more challenging. Our study aims at investigating whether local RFs based on one-only high b-value Diffusion Weighted (DW) sequence can stratify patients according to four classes with progressive PCa risk levels. 42 biopsy-proven patients were enrolled, including patients with negative biopsy and either negative (n=7) or positive (n=10) mpMRI, NCS-PCa (n=10), and CS-PCa (n=15). 84 RFs measuring local heterogeneity were extracted from DW$\mathrm{I}_{b2000}$, ranked based on Kruskal-Wallis (p$\lt$0.001) and one-tail Wilcoxon rank-sum test (p$\leq$0.05) for multi- and pair-wise comparisons. RFs stability was assessed as segmentations varied. The Spearman index $(\rho_{\mathrm{s}})$ assessed the rank correlation between RFs and risk levels. One RF, CVL-m, stratifies patients in 4 progressive classes with $\rho_{\mathrm{s}}=0.81$, thus suggesting that a progressive local tissue heterogeneity can predict PCa prognosis.

Bone metastases (BM) are still the main cause of morbidity and mortality in cancer patients, not only because of their complications, defined as skeletal-related events (SREs), but also because of the negative impact bone pain has on quality of life (QoL) and survival, especially when opioid analgesics and locoregional treatments fail.A single-center prospective study was carried out on 12 patients with symptomatic BM treated with MRI-guided focused ultrasound (MR-HIFU). The primary endpoint was the effectiveness of MR-HIFU in reducing current and breakthrough cancer pain (BTCP) scores. The main secondary aims were the evaluation of circulating markers at different time-points and their relation to pain and procedure efficacy. Other secondary objectives included temporal evolution of pain response, evaluation of QoL, and side effects of the treatment. Descriptive statistics were used to evaluate primary and secondary endpoints. Questionnaires on pain and QoL completed at baseline and at 30 days were compared using appropriate statistical tests with exploratory intent.MR-HIFU was successfully completed in all 12 patients enrolled between September 2015 and December 2018. On day 30, 6 (50.0%) patients showed a complete response of current pain and 6 a partial response, while 5 (41.7%) obtained a complete BTCP response. A partial response of BM evaluated by MD Anderson criteria was obtained in 9 (81.8%) patients. Only one patient progressed in the target lesion after MR-HIFU. No treatment-related adverse events were recorded. Bone turnover markers CTX/RANK-L (P) do not demonstrate any significant change with the pain or BM response.In our patients, targeted therapy of painful BM with MRI-guided focused ultrasound ablation was safe and showed encouraging early-onset and functional results.

Objective: Computed Tomography perfusion (CTp) of liver is very attractive for predictive and prognostic purposes, but motion artefacts and radiation dose connected to duration of examinations jeopardize the reproducibility of perfusion values, thwarting CTp daily application in clinics. The goal is showing to what extent these issues can be faced by shortening the CTp unenhanced stage (i.e., the baseline). Methods: 59 patients with colorectal cancer underwent undelayed hepatic CTp examinations. For each patient, fifteen virtual examinations E τ simulating different scan delays τ ∈ [1..15] s were achieved from the undelayed original sequence E 0 . Absolute (AD), percentage (PD) and compound differences ( CD τ ) were computed between E 0 and each E τ for baseline and perfusion values and measured in HU and arbitrary units (a.u.), respectively. Patients were grouped and counted based on the differences achieved. Results: Maximum perfusion CD τ 10 a.u. and baseline CD τ 7 HU were achieved. For τ ≤ 10 s, maximum perfusion CD τ ∈ [5,6) a.u. was found in one patient only as well as maximum baseline CD τ ∈ [2,3) HU. Blood flow (BF), hepatic perfusion index and arterial BF showed the lowest CD τ , while portal BF and total BF the highest ones. PD is practically always higher than AD. Conclusion: The approach presented allows clinicians to design the shortest CTp acquisition protocol, selecting the highest delay compliant with the required accuracy for the chosen perfusion parameters, to limit patient’s motion and improve image quality. Significance: A short CTp protocol allows strengthening the reliability of perfusion values, and correctness of clinical outcomes, advancing CTp introduction in the standard clinical practice.

Purpose: To discriminate between patients with high-risk (HR) and low-risk (LR) prostate cancer (PCa) in order to support radiologists in deciding on the most proper therapy strategy. Materials and Methods: 42 patients with a clinical suspicion of PCa were consecutively selected from the database of our institution. All patients underwent 3T-mpMRI and TRUS biopsy, and based on their Gleason Scores (GS) were assigned to HR (GS≥3+4) or LR class, the latter including, besides patients with GS=3+3, patients with a negative biopsy, whether they have positive or negative mpMRI. 84 radiomic features were extracted on DWI sequences and related ROC curves computed. The feature showing the lowest p-value in discriminating HR from LR was selected. Results: The mean of local coefficient of variation (CVL-m), representing local DWI variance, performed the best (p~10-6) and discriminates HR from LR with AUC=0.91 (95% CI, 0.75-0.97), specificity=85%, sensitivity=87% (4 FP and 2 FN), and all FPs are GS=3+3. These results yielded the probability of FDR=24% of the overtreatment for LR patients and probability of FOR=8% that a HR patient is not treated. Conclusions: One of our radiomic features derived from DWI sequences was enough to differentiate HR- from LR- PCa. Since the level of restriction to the motion of water molecules in the extracellular compartment affects tumour behaviour, radiomic features extracted from DWI sequences result in the best candidate to quantify relevant properties of tumour habitats needed to characterize the different tumour heterogeneities. Limitations: Patients were not enough to reliably include clinical parameters in the PCa risk assessment. Although they could be crucial to help to improve the radiomic model, a higher number of parameters requires a number of patients growing exponentially to have a representative sample size. Ethics committee approval: IRB approval, written informed consent was waived. Funding: No funding was received for this work.

Purpose Methods and materials Results Conclusion Personal information and conflict of interest References, Purpose: Active surveillance (AS) is the recommended approach for patients diagnosed with low-risk or indolent Prostate Cancer (PCa), but requires patients being timely monitored in order to identify early signs of PCa progression [1]. This study aims at...

Purpose: To investigate whether radiomic features computed on high b-value DWI sequences referring to tumour cellularity correlate with the 68GA-PSMA PET/CT ligand, highly specific for the diagnosis of prostate cancer (PCa). Materials and Methods: This study retrospectively enrols 17 patients belonging to a multi-cohort investigation for clinical impact of 3T-mpMRI and 68GA-PSMA PET/CT in PCa diagnosis and staging. PCa lesions were contoured in consensus by two-experienced radiologists in either DWI or T2w sequences, depending on where they were more visible. 40% of SUVmax was used as the threshold to contour lesions on PET images and, on these regions, the median of last decile of SUV (SUVM90th) was computed. Instead, 84 radiomic features were computed on b-2000 DWI lesions and their value was correlated to SUVM90th through absolute Spearman index (ρ). Results: Several radiomic features showed excellent correlations with 68GA-PSMA-SUVM90th. In particular, the radiomic feature performing as the best is related to local tumour heterogeneity and showed ρ≥0.7 in 82% of patients, ρ≥0.5 in just two cases, and one-only patient yielded ρ=0.3. Conclusions: The outcome reveals a rank correlation between degrees of PCa cellularity heterogeneity and 68GA- PSMA -SUVM90th. In other words, a wider expression of membrane receptors for PSMA seems corresponding to an over-proliferation of cells, which theoretically is suggestive of tumour onset and malignancy progression. Limitations: A wider cohort of patients is needed to better understand this correlation and to deepen the physiological and biomolecular causes of such behaviour.

Purpose: To assess to what extent radiomic features computed on high b-value DWI sequences (b=2000s/mm2) could reliably detect non-clinically significant (NCS) prostate cancer and reduce overtreatment. Materials and Methods: This study retrospectively enrolled 25 patients of our institution, randomly extracted from PACS with clinical suspicion of PCa who underwent prostate 3T-mpMRI. 10 patients reported NCS-PCa after TRUS biopsy, with Gleason Score (GS)≤3+3, 15 were CS-PCa. PCa Regions of Interest (ROIs) were outlined in all slices by two experienced radiologists in consensus and reported on the DWI sequences, when needed, where 84 radiomic features with the corresponding ROC curves were computed. In order to prevent overfitting, a one-only feature was selected yielding the highest AUC and p-value

Purpose: To investigate the potential role of radiomic features computed on high b-value Diffusion Weighted Imaging (DWI) to perform risk stratification of patients with a clinical suspicion of prostate cancer (PCa). Materials and Methods: 42 patients of our institution, representing 7 risk levels, were retrospectively enrolled in the study and grouped into 4 classes of risk: (a) clinically significant (CS) PCa, split over 4 levels (ISUP=2÷5), (b) non-clinically significant (NCS) PCa (ISUP=1), patients with a negative biopsy and (c) positive mpMRI (NP) or (d) negative mpMRI (NN). After computing radiomic features on DWI b=2000s/mm2, the correlation between radiomic features and risk level was investigated through two steps: (i) Spearman index (ρ), (ii) Kruskal-Wallis and Wilcoxon tests (p

Cancer is a risk factor for venous thromboembolism (VTE). Plasma tumor DNA (ptDNA) is an independent predictor of outcome in metastatic castration-resistant prostate cancer (mCRPC). We aimed to investigate the association between ptDNA and VTE in mCRPC. This prospective biomarker study included 180 mCRPC patients treated with abiraterone and enzalutamide from April 2013 to December 2018. We excluded patients with a previous VTE history and/or ongoing anticoagulation therapy. Targeted next-generation sequencing was performed to determine ptDNA fraction from pretreatment plasma samples. VTE risk based on survival analysis was performed using cumulative incidence function and estimating sub-distributional hazard ratio (SHR). At a median follow-up of 58 months (range 0.5-111.0), we observed 21 patients who experienced VTE with a cumulative incidence at 12 months of 17.1% (95% confidence interval [CI] 10.3-23.9). Elevated ptDNA, visceral metastasis, prior chemotherapy and lactate dehydrogenase (LDH) were significantly associated with higher VTE incidence compared to patients with no thrombosis (12-month estimate, 18.6% vs 3.5%, P = .0003; 44.4% vs 14.8%, P = .015; 24.7% vs 4.5%, P = .006; and 30.0% vs 13.5%, P = .05, respectively). In the multivariate analysis including ptDNA level, visceral metastases, number of lesions and serum LDH, high ptDNA fraction was the only independent factor associated with the risk of thrombosis (HR 5.78, 95% CI 1.63-20.44, P = .006). These results first suggest that baseline ptDNA fraction in mCRPC patients treated with abiraterone or enzalutamide may be associated with increased VTE risk. These patients may be followed-up more closely for the VTE risk, and the need for a primary thromboprophylaxis should be taken into account in mCRPC with elevated ptDNA.

In Italy, the first case of the coronavirus disease 2019 (COVID-19) was officially reported on 20.02.2020. The disease has since rapidly evolved, causing a public health emergency throughout the country but especially in our region, one of the most widely affected areas. We reorganized the daily routine of our cancer center to reduce the risk of contagion. A temporary tensile structure was set up as an entry-point triage, and a COVID-19 route was created with a dedicated CT scanner. A pre-access telephonic triage was performed the day before a patient was scheduled to come in for an examination. At the time of writing (May 4), 4053 patients had been to our center since the emergency officially began (9.03.2020) and the COVID-19 route had been activated for only 9 paucisymptomatic outpatients and 7 symptomatic inpatients. We also re-evaluated patient radiology examination lists and rescheduled non-urgent tests in consensus with the referring oncologist. Out of a total of 1438 patients scheduled for radiological examinations, 456 were postponed for a total volume reduction of 29.1%. Nine asymptomatic patients with typical CT findings of COVID-19 were identified during routine CTs, but none were RT-PCR-positive for SARS-CoV-2. We guaranteed all urgent and semi-urgent examinations, including those to stage newly diagnosed cancers and to evaluate response to treatment, ensuring the continuation of the diagnostic and therapeutic pathway of our patients. The measures we took were instrumental in keeping the institute COVID-19-free. We also describe the planned measures to resume normal clinical practice at the center.

Background Posterior reversible encephalopathy syndrome (PRES) is a condition characterized by seizures, headache, visual disturbances, paresis, nausea and altered mental status. Risk factors include hypertension, eclampsia/pre-eclampsia, infection/sepsis, transplantation (allograft, bone marrow and solid organ) and immunosuppression, especially in association with autoimmune disorders and use of cyclosporine or chemotherapy. Case report A few days after starting the first cycle of treatment with capecitabine, a 50-year-old female with metastatic breast cancer experienced serious adverse events consisting of severe hematological, gastrointestinal and neurological toxicity. A brain magnetic resonance imaging, performed because of the severe state of confusion of the patient, confirmed PRES. Management and outcome The patient was admitted to the hospital; capecitabine was stopped and treatment was started with antibiotics, growth factor therapy and blood and platelet transfusions. Her clinical conditions slowly improved and the PRES resolved. A dihydropyrimidine dehydrogenase deficiency was identified. Discussion The patient had previously been treated with another fluoropyrimidine, 5-fluorouracil, but without toxicity. A literature search was performed, and only six cases of PRES associated with capecitabine were found. Our case suggests that capecitabine differs from 5-fluorouracil in its mechanism of action and that at least one of the metabolites of capecitabine has the ability to cross the blood–brain barrier, causing neurotoxicity. We believe that it is useful to test for dihydropyrimidine dehydrogenase deficiency before using fluoropyrimidines and would encourage the reporting of such cases of PRES to gain a better overall picture of its incidence in this setting. Naranjo score 7

152 Background: Accurate monitoring response of bone mets to treatment is an active need for mCRPC patients (pts). Recently, ctDNA has been showed as an early biomarker efficacy of androgen receptor signaling inhibitor (ARSI) therapy for mCRPC ( Conteduca, Br J Cancer 2020). In this study, we aimed to reveal if ctDNA analysis can permit more reliable prediction of bone mets burden and radiographic progression disease (PD). Methods: In a biomarker study (REC 2192/2013), targeted next generation sequencing was performed to assess ctDNA fraction. Radiographic evidence of bone disease was documented by conventional imaging according to PCWG3 criteria ( Scher, J Clin Oncol 2018), and was classified on the basis of mets number (≤5, 6 -19, ≥20) in oligometastatic (O), diffuse (D), and widespread (W), respectively. Associations were explored both through uni/multivariate logistic regressions. Results: Serial plasma samples and radiographic scans on ARSI treatment were prospectively collected from 73 CRPC with bone mets. Median age was 74 years [interquartile range (IQR) 69-79]. Bone mets patterns were significantly associated with median baseline ctDNA level (O = 0.16, D = 0.33, and W = 0.46, p 0.0003). Similar results were reported on treatment and at PD (p 0.0003 and p 0.0007, respectively). In 24 pts with a progressive worsening of bone mets pattern (O→D→W) compared to pts with no change in bone mets pattern on ARSI, we observed an early meaningful ctDNA rise with a % ctDNA variation from baseline to 3 month therapy of 150.6% (IQR 104.9-210.7) vs 11.1% (IQR 0-36.6), p < 0.0001. Univariate analysis showed that early ctDNA rise was significantly associated with radiographic progression free/overall survival (rPFS/OS): hazard ratio (HR) 2.06, 95% confidence interval (CI) 1.30-3.27, p 0.002, and HR 1.82, 95% CI 1.15-2.88, p 0.01, respectively]. In multivariable analyses including ctDNA variation, changing bone mets pattern, age, performance status, and presence of concomitant visceral mets, ctDNA change at 3 month ARSI resulted the only independent predictor of both rPFS/OS (HR 2.27, 95% CI 1.04-4.94, p 0.027 and HR 2.98, 95% CI 1.31-6.81, p 0.033, respectively). Visceral mets were associated with only OS (HR 3.87, 95% CI 1.76-8.51, p 0.0008). Conclusions: Early ctDNA variation may reflect changes in bone mets pattern on ARSI allowing to track pattern of bone progression and predict outcome. Further studies to validate these findings are warranted.

Introduction: 68Ga-PSMA is a labelled ligand to a membrane protein overexpressed in many prostate cancer cells and has raised its interest to be highly specific in PET imaging for detection and staging of prostate cancers. DW-MRI is a standard technique that provides quantitative information about tumor cellularity and tissue structure is a useful tool for the detection and staging of prostate cancer in clinical practice. This study investigates the correlation between SUVmax and tumour heterogeneity computed from DWI sequences. Materials and Methods: 17 patients (age range, 49-75 years; mean, 64.3 years) of a prospective study aiming at multi-cohort investigation for clinical impact of mp-3TMRI and 68Ga-PSMA PET/CT in diagnosis of clinically-significant prostate cancer and presurgical staging. After co-registering MRI and PET sequences, Regions of Interest (ROIs) were manually delineated around prostate in MRI/T2 and the cancer lesion in the dominant sequence (high values of DWI or T2). SUVmax was computed on PET images and 60%-threshold of SUVmax was used for lesion contouring. A compound texture feature related to tumour heterogeneity (Hc) was computed within prostate ROIs in DWI and the outcome represented with colorimetric maps. The highest regions were extracted by automatic contouring. Average Hc (DWI) and SUVmax (PET) were computed on the co-registered slices and the Spearman rank correlation (ρ) was assessed. Results: SUVmax ranges from [1.6-101.0] and Hc through [37.9 -50.6]. Regions highlighted by Hc are usually much greater than those detected by SUVmax thresholding and always include the region outlined by radiologists. 13 patients show ρ≥0.7, 3 with ρ≥0.5 and 1 only with ρ≥0.25. For 11 patients (65% of cases) the amount of PET slices pointing out malignant SUV peaks is greater than DWI slices showing high Hc values, with Hc ROIs better depicting tumour extent. For 3 patients (17.5%) PET and Hc-DWI show equivalent performance in tumour detection and in 3 cases only, Hc points out more slices with suspect tumour ROIs. However, in all cases SUV and Hc show the same trend, with the highest values around central slices and a much greater increasing rate for SUV. Conclusions: The outcomes of this study reveal a rank correlation between heterogeneity of cellularization and the expression of the membrane receptor of PSMA. The reason of such correlation requires deeper investigations and could be confirmed after examining a wider cohort. Hc result a promising compound feature for outlining malignant ROIs extent to be employed together with PET sequences for validating tumour side. A deeper analysis is required for those few cases showing weak or even poor correlation between SUV and Hc.

Introduction: Palliative care (PC) aims to treat symptoms independently of the disease. In many medical disciplines, including oncology, there is an emphasis on personalizing treatment, identifying the most effective therapeutic option by studying the genetic heritage of the patient and the molecular characteristics of the disease. PC, on the other hand, encompasses the overall (physical and spiritual) well-being of the patient and his or her caregivers. The increasing use of early PC and its integration with oncology could represent a fruitful collaboration among specialists. Case description: We present the case of a 79-year-old woman with advanced breast cancer attending our institute who was referred to our PC Unit because of continuous ear pain, paresthesia around the mouth, strabismus, and facial dysesthesia. The patient was in good clinical condition (Eastern Cooperative Oncology Group 1) and was undergoing chemotherapy at the time. For these reasons, the PC physician carefully assessed the pain characteristics and differential diagnosis and discussed them with the oncologist, radiologist, and neurologist. Joint consultation led to a specific study of Meckel cave by MRI, revealing an extrameningeal gasserian ganglion metastasis, a very rare localization of breast cancer. Conclusion: We present a case that underlines the importance of specialized PC assessment not limited to the control of symptoms. The search for the etiopathogenesis of a patient’s symptoms and the evaluation of overall clinical conditions may be necessary to plan appropriate diagnostic evaluations, target palliative therapies, and achieve effective symptom control.

5048 Background: Cancer is a risk factor for VTE. In mCRPC, ptDNA is an independent predictor of outcome ( Romanel, Sci Transl Med 2015; Conteduca, Br J Cancer 2020). We firstly aimed to investigate the association between ptDNA and VTE in mCRPC men treated with androgen receptor signaling inhibitors (ARSI) Methods: This prospective biomarker study included mCRPC patients treated with abiraterone and enzalutamide from April 2013 to December 2018. We excluded patients with a previous VTE history and/or ongoing anticoagulation. Targeted next-generation sequencing was performed to determine ptDNA fraction from pre-treatment plasma samples. Assessment of VTE risk based on survival analysis was performed using cumulative incidence function and estimating sub-distributional hazard ratio (SHR) Results: Median age of 180 enrolled patients was 74 years (range 42-90). Of these, 60 (33.3%) were chemotherapy-naive. At a median follow-up of 58 months (range 0.5-111.0), 21 patients experienced VTE (venous thrombosis and/or pulmonary embolism) with a cumulative incidence of VTE at 12 months of 17.1% (95% CI 10.3-23.9). Before starting ARSI, ptDNA fraction above median value of 0.175, presence of visceral metastasis (mets), prior chemotherapy and serum lactate dehydrogenase (LDH) were significantly associated with higher incidence of VTE compared with patients with no thrombosis (12-month estimate, 18.6 vs 3.5%, P=0.0003; 44.4 vs 14.8%, P=0.015; 24.7 vs 4.5%, P=0.006; and 30.0 vs 13.5%, P=0.050, respectively). In the multivariate analysis (Table) including baseline ptDNA level, visceral, liver and lung mets, number of lesions, LDH, high ptDNA fraction was the only independent factor associated with the risk of thrombosis (HR 5.78, 95% confidence interval [CI] 1.63-20.44, P=0.006). All these patients received anticoagulant therapy for VTE. No ARSI discontinuation and VTE-related death were reported, and no significant difference in progression-free/overall survival was observed in mCRPC patients with and without VTE. Conclusions: These results suggest that baseline ptDNA fraction in mCRPC patients treated with ARSI is associated with increased risk of VTE. These patients may be followed up more closely for the risk of VTE and the need for a primary thromboprophylaxis should be taken into account in mCRPC with elevated ptDNA concentration. Validation of these findings in larger multicenter trials is warranted.[Table: see text]

Rationale and Objectives To study the effects of four different rigid alignment approaches on both time-concentration curves (TCCs) and perfusion maps in computed tomography perfusion (CTp) studies of liver and lung tumors. Materials and Methods Eleven data sets in patients who were subjected to axial CTp after contrast agent administration were assessed. Each data set consists of four different sequences, according to the different rigid alignment configurations considered to compute blood flow perfusion maps: no alignment, translational, craniocaudal, and three dimensional (3D). The color maps were built on TCCs according to the maximum slope method. The effects of motion correction procedures on the reliability of TCCs and perfusion maps were assessed both quantitatively and visually. Results TCCs built after 3D alignments show the best indices as well as producing the most reliable maps. We show examinations in which the translational alignment only yields more accurate TCCs, but less reliable perfusion maps, than those achieved with no alignment. Furthermore, we show color maps with two different perfusion patterns, both considered reliable by radiologists, achieved with different motion correction approaches. Conclusions The quantitative index we conceived allows relating quality of 3D alignment and reliability of perfusion maps. A better alignment does not necessarily yield more reliable perfusion values: color maps resulting from either alignment procedure must be critically assessed by radiologists. This achievement will hopefully represent a step forward for the clinical use of CTp studies for staging, prognosis, and monitoring values of therapeutic regimens.

Background No compelling evidence is available about surveillance and follow-up of patients with testicular germ cell tumour (TGCT). Methods In the light of the best clinical evidence, the Italian Germ cell cancer Group (IGG) and the Associazione Italiana di Oncologia Medica (AIOM) set up a multidisciplinary national consensus conference, involving 42 leading experts and 3 TGCT survivors. A minimum of 50% of votes was required in order to achieve a consensus recommendation on 29 questions. Results Recommendations have been summarized in three tables, divided by stage I seminoma, stage I nonseminoma and the advanced disease, which may be useful for clinicians to appropriately choose the clinical investigation and its timing during the surveillance and follow-up of TGCT patients based on an accurate estimation of their risk of disease relapse. Conclusions The IGG-AIOM consensus recommendations may help clinicians to choose appropriate clinical investigations for the surveillance and follow-up of TGCT patients.

In the last few years, cancer treatments have improved significantly with the introduction of new therapies aiming at reducing tumour angiogenesis, a process leading to disease progression and metastasis formation. Computed tomography perfusion (CTp) is being emerged as a promising functional technique for assessing tumour response to these new treatments, which yield a reduction of perfusion heterogeneity, occurring long before morphological reduction. However, several factors, such as noise induced by respiratory and physiological involuntary motion, prevent a reliable quantitative assessment, hence the clinical use of CTp. Currently, the assessment strategies rely on global measurements that fail in discriminating between noise and heterogeneity of tumour perfusion, both characterized by a wide value dispersion. This paper presents a new approach for reliability estimation by introducing a novel local-based index, which is able to discriminate between tumour heterogeneity, featured by locally structured patterns, and noise, characterised by sparse and unstructured values. This index enables a proper comparison between perfusion maps and can replace the parameters based on the global mean, thus improving the overall reliability of CTp studies and favouring the translation into clinical routine.

Purpose Methods and materials Results Conclusion Personal information References, Purpose: Currently, diagnosis and monitoring of lung cancer mainly rely on a visual based morphological analysis [1], primarily performed with computed tomography (CT). Assessment of treatment effects of conventional chemotherapeuticals are visually...

We studied the usefulness of 68Ga-prostate-specific membrane antigen (PSMA) PET/CT for detecting relapse in a prospective series of patients with biochemical recurrence (BCR) of prostate cancer (PCa) after radical treatment. Patients with BCR of PCa after radical surgery and/or radiotherapy with or without androgen-deprivation therapy were included in the study. 68Ga-PSMA PET/CT scans performed from the top of the head to the mid-thigh 60 min after intravenous injection of 150 ± 50 MBq of 68Ga-PSMA were interpreted by two nuclear medicine physicians. The results were correlated with prostate-specific antigen (PSA) levels at the time of the scan (PSApet), PSA doubling time, Gleason score, tumour stage, postsurgery tumour residue, time from primary therapy to BCR, and patient age. When available, 68Ga-PSMA PET/CT scans were compared with negative 18F-choline PET/CT scans routinely performed up to 1 month previously. From November 2015 to October 2017, 314 PCa patients with BCR were evaluated. Their median age was 70 years (range 44–92 years) and their median PSApet was 0.83 ng/ml (range 0.003–80.0 ng/ml). 68Ga-PSMA PET/CT was positive (one or more suspected PCa lesions detected) in 197 patients (62.7%). Lesions limited to the pelvis, i.e. the prostate/prostate bed and/or pelvic lymph nodes (LNs), were detected in 117 patients (59.4%). At least one distant lesion (LNs, bone, other organs, separately or combined with local lesions) was detected in 80 patients (40.6%). PSApet was higher in PET-positive than in PET-negative patients (P

To investigate early changes in tumour perfusion parameters by dynamic contrast-enhanced ultrasonography (D-CEUS) and to identify any correlation with survival and tumour response in patients with metastatic colorectal cancer (CRC) treated with bevacizumab (B). Thirty-seven patients randomized to either chemotherapy (C) plus B or C alone were considered for this study. D-CEUS was performed at baseline and after the first treatment cycle (day 15). Four D-CEUS perfusion parameters were considered: derived peak intensity (DPI), area under the curve (AUC), slope of wash-in (A) and time to peak intensity (TPI). In patients treated with C plus B, a ≥22.5 % reduction in DPI, ≥20 % increase in TPI and ≥10 % reduction in AUC were correlated with higher progression-free survival in the C+B arm (p = 0.048, 0.024 and 0.010, respectively) but not in the C arm. None of the evaluated parameter modifications had a correlation with tumour response or overall survival. D-CEUS could be useful for detecting and quantifying dynamic changes in tumour vascularity as early as 15 days after the start of B-based therapy. Although these changes may be predictive of progression-free survival, no correlation with response or overall survival was found. • D-CEUS showed early changes in liver metastasis perfusion in colorectal cancer. • A decrease in tumour perfusion was associated with longer progression-free survival. • The decrease in perfusion was not correlated with higher overall survival.

Prostate cancer is one of the most common malignant neoplasms in men worldwide, and is the fifth cause of cancer-related death. In recent years, a new generation of therapies have been approved for the management of metastatic disease. Moreover, the development of new immunotherapeutic drugs has become a novel frontier for the treatment of several tumor types; to date, numerous studies have investigated their potential activity, including in prostate cancer. In this article, we discuss the role of emerging immunotherapeutic drugs in prostate cancer patients.

A previous study showed that a tolerogenic gene vaccine based on a IgG1Fc-pCons chimera (here named GX101) protects NZB/NZW mice from SLE development. The present study was aimed at identifying the most effective schedule of immunization and the possible involvement of CD4(+) Foxp3(+) Treg in the mechanism of action, in view of its eventual translation to the human studies. NZB/NZW mice were vaccinated with B lymphocytes made transgenic by spontaneous transgenesis with a gene coding for a chimeric IgG1Fc-pCons construct. Different schedules of vaccination were set in relation to the timing and number of administrations. Survival, proteinuria levels, and CD4(+) Foxp3(+) Treg frequency were monitored during the full experiments. GX101-treated mice showed delayed disease onset and delayed mortality than controls. GX101 effects were implemented by early as well as repeated vaccine administrations. GX101 vaccination was associated with increased frequencies of CD4(+) CD25(+) Foxp3(+) Treg with respect to controls. This study demonstrates that early and repeated immunizations with GX101 vaccine provide a better outcome than late or single vaccine administration regarding onset/development in SLE-prone mice, acting as a possible disease-modifying approach. Vaccine effects are likely related to CD4(+) Foxp3(+) Treg cell expansion.

Objectives To correlate the radiologic findings detected with computed tomography scan with anthropological data in 13 naturally mummified bodies discovered during works of recovery of an ancient church in a crypt in Roccapelago, in the Italian Apennines. Methods From a group of about sixty not-intentionally mummified bodies, thirteen were selected to be investigated with volumetric computed tomography (CT). Once CT scan was performed, axial images were processed to gather MPR and Volume Rendering reconstructions. Elaborations of these images provided anthropometric measurements and a non-invasive analysis of the residual anatomical structures. For each body the grade of preservation and the eventual pathological changes were recorded. Furthermore, in order to identify nutritional and occupational markers, radiologic signs of bone tropism and degenerative changes were analysed and graded. Results Mummies included seven females and six males, with an estimated age ranging from 20 to 60 years. The first relevant finding identified was a general low grade of preservation, due to the lack of anatomic tissues different from bones, tendons and dehydrated skin. The low grade of preservation was related to the natural process of mummification. Analysing bone degenerative changes on CT scan, the majority of the bodies had significant occupational markers consisting of arthritis in the spine, lower limbs and shoulders even in young age. Few were the pathological findings identified. Among these, the most relevant included a severe bilateral congenital hip dysplasia and a wide osteolytic lesion involving left orbit and petrous bone that was likely the cause of death. Conclusions Although the low grade of preservation of these mummies, the multidisciplinary approach of anthropologists and radiologists allowed several important advances in knowledge for the epidemiology of Roccapelago. First of all, a profile of living conditions was delineated. It included occupational and nutritional conditions. Moreover, identification of some causes of death and, most importantly the definition of general living conditions.

Aims and objectives Methods and materials Results Conclusion Personal information References, Aims and objectives: Computed Tomography perfusion (CTp) represents a promising imaging technique in the oncological field, expectedly providing information in diagnosis, to discriminate benign from malignant lesions [1], tumour staging [2] and prognosis [3]....

none 4 no Objectives: Tumour heterogeneity represents a key issue in CT perfusion (CTp), where all studies are usually based on global mean or median values of perfusion maps, often computed on whole tumour. We sought to determine whether, and to what extent, such global values can be representative of tumour heterogeneity, with respect to single slices, and could be used for therapy assessment. Materials and Methods: Twelve patients with one primary non-small cell lung cancer lesion were enrolled in this study, for a total amount of 26 CTp examinations and 118 slices. Mean and median blood flow (BF) values, calculated voxel-based, were computed on each slice and the whole tumour. To measure functional heterogeneity, entropy was calculated on BF values as well. Results: Most of the slices were not represented by the global BF values computed on the whole tumour. In addition, there is a number of lesions having equivalent global BF values, but composed by slices having very different heterogeneity distributions, that is, entropy values. Conclusions: Global mean/median BF values of the single slices separately should be considered for clinical assessment, only if interpreted through entropy computed on BF values. The numerical equivalence between global BF values of different lesions may correspond to different clinical status, thus inducing possible errors in choice of therapy when considering global value only. none Malavasi, Silvia; Barone, Domenico; Gavelli, Giampaolo; Bevilacqua, Alessandro Malavasi, Silvia; Barone, Domenico; Gavelli, Giampaolo; Bevilacqua, Alessandro

Background: Preliminary studies suggest beneficial effects of animal-assisted activities (AAA) on behavioral and psychological symptoms of dementia (BPSD), but data are inconsistent. This study aimed to assess the effect of AAA with dogs on cognition, BPSD, emotional status and motor activity in severe Alzheimer's disease (AD).Methods: Ten patients attending an Alzheimer Day Care Center (ADCC) participated in a repeated measures study, which included: two weeks' pre-intervention, three weeks' control activity with plush dogs (CA), and three weeks' AAA. Cognitive function (Severe Impairment Battery), mood (Cornell Scale for Depression in Dementia; CSDD), BPSD (Neuropsychiatric Inventory; NPI) and agitation (Cohen-Mansfield Agitation Inventory; CMAI) were assessed at baseline and after each period. Observed Emotion Rating Scale (OERS) for emotional status, Agitated Behavior Mapping Instrument (ABMI) and a checklist for motor activity were completed across the study periods, both during intervention sessions and after three hours.Results: Cognition and NPI were unchanged across the study. Declines in the CMAI and CSDD scores after AAA were not significant, while the NPI anxiety item score decreased in comparison with CA (CA 3.1±2.3, AAA 1.5±2.7, p = 0.04). OERS “sadness” decreased (p = 0.002), while “pleasure” (p = 0.016) and “general alertness” (p = 0.003) increased during AAA compared with CA sessions, and observed sadness remained lower after three hours (p = 0.002). Motor activity increased significantly during AAA.Conclusion: In this sample of severe AD patients in ADCC, AAA was associated with a decrease in anxiety and sadness and an increase in positive emotions and motor activity in comparison with a control activity.